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Background: The existence of sociodemographic disparities in pancreatic cancer has been well-studied but how these disparities have changed over time is unclear. The purpose of this study was to longitudinally assess patient management in the context of sociodemographic factors to identify persisting disparities in pancreatic cancer care., Methods: Using the National Cancer Database, patients diagnosed with pancreatic ductal adenocarcinoma from 2010 to 2017 were identified. The primary outcomes were surgical resection and/or receipt of chemotherapy. Outcome measures included changes in associations between sociodemographic factors (i.e., sex, age, race, comorbidity index, SES, and insurance type) and treatment-related factors (i.e., clinical stage at diagnosis, surgical resection, and receipt of chemotherapy). For each year, associations were assessed via univariate and multivariate analyses., Results: Of 75,801 studied patients, the majority were female (51%), White (83%), and had government insurance (65%). Older age (range of OR 2010-2017 [range-OR]:0.19-0.29), Black race (range-OR: 0.61-0.78), lower SES (range-OR: 0.52-0.94), and uninsured status (range-OR: 0.46-0.71) were associated with lower odds of surgical resection (all p < 0.005), with minimal fluctuations over the study period. Older age (range-OR: 0.11-0.84), lower SES (range-OR: 0.41-0.63), and uninsured status (range-OR: 0.38-0.61) were associated with largely stable lower odds of receiving chemotherapy (all p < 0.005)., Conclusions: Throughout the study period, age, SES, and insurance type were associated with stable lower odds for both surgery and chemotherapy. Black patients exhibited stable lower odds of resection underscoring the continued importance of mitigating racial disparities in surgery. Investigation of mechanisms driving sociodemographic disparities are needed to promote equitable care., (© 2024 International Society of Surgery/Société Internationale de Chirurgie (ISS/SIC).)

Background: Fluorodeoxyglucose uptake on positron emission tomography imaging has been shown to be an independent risk factor for malignancy in thyroid nodules. More recently, a new positron emission tomography radiotracer-Gallium-68 DOTATATE-has gained popularity as a sensitive method to detect neuroendocrine tumors. With greater availability of this imaging, incidental Gallium-68 DOTATATE uptake in the thyroid gland has increased. It is unclear whether current guideline-directed management of thyroid nodules remains appropriate in those that are Gallium-68 DOTATATE avid., Methods: We retrospectively reviewed Gallium-68 DOTATATE positron emission tomography scans performed at our institution from 2012 to 2022. Patients with incidental focal Gallium-68 DOTATATE uptake in the thyroid gland were included. Fine needle aspiration biopsies were characterized via the Bethesda System for Reporting Thyroid Cytopathology. Bethesda III/IV nodules underwent molecular testing (ThyroSeq v3), and malignancy risk ≥50% was considered positive., Results: In total, 1,176 Gallium-68 DOTATATE PET scans were reviewed across 837 unique patients. Fifty-three (6.3%) patients demonstrated focal Gallium-68 DOTATATE thyroid uptake. Nine patients were imaged for known medullary thyroid cancer. Forty-four patients had incidental radiotracer uptake in the thyroid and were included in our study. Patients included in the study were predominantly female sex (75%), with an average age of 62.9 ± 13.9 years and a maximum standardized uptake value in the thyroid of 7.3 ± 5.3. Frequent indications for imaging included neuroendocrine tumors of the small bowel (n = 17), lung (n = 8), and pancreas (n = 7). Thirty-three patients underwent subsequent thyroid ultrasound. Sonographic findings warranted biopsy in 24 patients, of which 3 were lost to follow-up. Cytopathology and molecular testing results are as follows: 12 Bethesda II (57.1%), 6 Bethesda III/ThyroSeq-negative (28.6%), 1 Bethesda III/ThyroSeq-positive (4.8%), 2 Bethesda V/VI (9.5%). Four nodules were resected, revealing 2 papillary thyroid cancers, 1 neoplasm with papillary-like nuclear features, and 1 follicular adenoma. There was no difference in maximum standardized uptake value between benign and malignant nodules (7.0 ± 4.6 vs 13.1 ± 5.7, P = .106). Overall, the malignancy rate among patients with sonography and appropriate follow-up was 6.7% (2/30). Among patients with cyto- or histopathology, the malignancy rate was 9.5% (2/21). There were no incidental cases of medullary thyroid cancer., Conclusion: The malignancy rate among thyroid nodules with incidental Gallium-68 DOTATATE uptake is comparable to rates reported among thyroid nodules in the general population. Guideline-directed management of thyroid nodules remains appropriate in those with incidental Gallium-68 DOTATATE uptake., (Copyright © 2023 Elsevier Inc. All rights reserved.)

Mucinous cholangiocarcinoma is an extremely rare form of intrahepatic cholangiocarcinoma that has been characterized by rapid growth, widespread metastasis and poor prognosis. These tumors have been shown to be a part of the Lynch syndrome tumor spectrum, however, the role of DNA mismatch repair (MMR) deficiency in their development is poorly understood. We present the case of a 74-year-old male with cholangiocarcinoma, who underwent Roux-en-Y hepaticojejunostomy and extended left hepatectomy and was diagnosed with a primary small bowel adenocarcinoma 2 years later. Immunohistochemistry testing for mismatch repair proteins was significant for the loss of nuclear expression of PMS2. Taken together, the cause of both the mucinous cholangiocarcinoma and primary small bowel adenocarcinoma with PMS2 loss in the patient presented here is likely genetic, suggestive of a cancer syndrome., (Published by Oxford University Press and JSCR Publishing Ltd. All rights reserved. © The Author(s) 2022.)

Objective: The objective of this study was to test the hypothesis that distal pancreatectomy (DP) without intraperitoneal drainage does not affect the frequency of grade 2 or higher grade complications., Background: The use of routine intraperitoneal drains during DP is controversial. Prior to this study, no prospective trial focusing on DP without intraperitoneal drainage has been reported., Methods: Patients undergoing DP for all causes at 14 high-volume pancreas centers were preoperatively randomized to placement of a drain or no drain. Complications and their severity were tracked for 60 days and mortality for 90 days. The study was powered to detect a 15% positive or negative difference in the rate of grade 2 or higher grade complications. All data were collected prospectively and source documents were reviewed at the coordinating center to confirm completeness and accuracy., Results: A total of 344 patients underwent DP with (N = 174) and without (N = 170) the use of intraperitoneal drainage. There were no differences between cohorts in demographics, comorbidities, pathology, pancreatic duct size, pancreas texture, or operative technique. There was no difference in the rate of grade 2 or higher grade complications (44% vs. 42%, P = 0.80). There was no difference in clinically relevant postoperative pancreatic fistula (18% vs 12%, P = 0.11) or mortality (0% vs 1%, P = 0.24). DP without routine intraperitoneal drainage was associated with a higher incidence of intra-abdominal fluid collection (9% vs 22%, P = 0.0004). There was no difference in the frequency of postoperative imaging, percutaneous drain placement, reoperation, readmission, or quality of life scores., Conclusions: This prospective randomized multicenter trial provides evidence that clinical outcomes are comparable in DP with or without intraperitoneal drainage.

Background: Primary hyperparathyroidism is characterized by increased levels of serum calcium and parathyroid hormone. Recently, 2 additional mild biochemical profiles have emerged, normocalcemic and normohormonal primary hyperparathyroidism. We reviewed our surgical experience of mild biochemical profile patients and compared them with classic primary hyperparathyroidism patients., Methods: This is a single institution, retrospective cohort review of all patients who underwent parathyroidectomy for primary hyperparathyroidism from 2006-2012. Preoperative and intraoperative variables were analyzed. Univariable analysis was performed with analysis of variance and the χ 2 test. A logistic regression was performed to identify significantly independent predictor variables for multigland disease., Results: A total of 573 patients underwent parathyroidectomy for primary hyperparathyroidism (classic, n = 405; normohormonal, n = 96; normocalcemic, n = 72). Normocalcemic primary hyperparathyroidism was associated with multigland disease in 43 (45%, P < .001) patients as compared with the normohormonal (7, 10%) and classic (36, 9%) groups. On logistic regression, significant predictors for multigland disease were the normocalcemic subtype and positive family history. Twelve month biochemical normalization rates after operative treatment were >98% in all 3 groups., Conclusion: Our series shows that normocalcemic primary hyperparathyroidism is associated with a high incidence of multigland disease. Normohormonal disease is similar to classic disease patients with >90% presenting with single adenomas. Excellent rates of biochemical normalization can be obtained by operative treatment in all 3 groups., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Context: Endocrine and exocrine insufficiency after partial pancreatectomy affect quality of life, cardiovascular health, and nutritional status. However, their incidence and predictors are unknown., Objective: To identify the incidence and predictors of new-onset diabetes and exocrine insufficiency after partial pancreatectomy., Design: We retrospectively reviewed 1165 cases of partial pancreatectomy, performed from 1998 to 2010, from a large population-based database., Main Outcome Measures: Incidence of new onset diabetes and exocrine insufficiency RESULTS: Of 1165 patients undergoing partial pancreatectomy, 41.8% had preexisting diabetes. In the remaining 678 patients, at a median 3.6 months, diabetes developed in 274 (40.4%) and pancreatic insufficiency developed in 235 (34.7%) patients. Independent predictors of new-onset diabetes were higher Charlson Comorbidity Index (CCI; hazard ratio [HR] = 1.62 for CCI of 1, p = 0.02; HR = 1.95 for CCI ≥ 2, p < 0.01) and pancreatitis (HR = 1.51, p = 0.03). There was no difference in diabetes after Whipple procedure vs distal pancreatic resections, or malignant vs benign pathologic findings. Independent predictors of exocrine insufficiency were female sex (HR = 1.32, p = 0.002) and higher CCI (HR = 1.85 for CCI of 1, p < 0.01; HR = 2.05 for CCI ≥ 2, p < 0.01). Distal resection and Asian race predicted decreased exocrine insufficiency (HR = 0.35, p < 0.01; HR = 0.54, p < 0.01, respectively)., Conclusion: In a large population-based database, the rates of postpancreatectomy endocrine and exocrine insufficiency were 40% and 35%, respectively. These data are critical for informing patients' and physicians' expectations.

Objectives: Intraductal papillary mucinous neoplasms (IPMNs) are premalignant pancreatic cysts commonly found incidentally. Immunosuppression accelerates carcinogenesis.Thus, we aimed to compare IPMN progression in liver transplant (LT) recipients on chronic immunosuppression to progression among an immunocompetent population., Methods: We retrospectively assessed adult LT recipients between 2008 and 2014 for imaging evidence of IPMN. Diagnosis of IPMN was based on history, imaging, and cyst fluid analysis. The immunocompetent control group consisted of nontransplant patients from our pancreatic cyst surveillance program with IPMN under surveillance for greater than 12 months between 1997 and 2013. Four hundred fifty-four patients underwent LT in the study period and had cross-sectional imaging., Results: The prevalence of suspected IPMN was 6.6% (30 of 454). Compared with 131 controls, the transplant cohort was younger, with increased prevalence of diabetes and smoking. The prevalence of other risk factors for IPMN progression (history of pancreatitis, family history of pancreatic cancer) was similar. After an average follow-up of 31 months, most cysts increased in diameter, with a similar increase of dominant cyst (0.4 cm vs 0.5 cm; P = 0.6). Type of immunosuppression was not associated with the increased rate of cyst growth., Conclusions: Our findings suggest that LT recipients with incidental IPMN can be managed under similar guidelines as immunocompetent patients.

Objectives: This study compares the progression of multifocal (MF) intraductal papillary mucinous neoplasms (IPMNs) to unifocal (UF) lesions., Methods: We performed a retrospective review of demographics, risk factors, and cyst characteristics of a prospectively maintained database of 999 patients with pancreatic cysts. Patients included had IPMN under surveillance for 12 months or more. Those with high-risk stigmata were excluded. Cyst size progression and development of worrisome features were compared between MF and UF cohorts. We evaluated whether the dominant cyst in MF-IPMN had more significant growth than did the other cysts., Results: Seventy-seven patients with MF-IPMN and 54 patients with UF-IPMN, with mean follow-up of 27 and 34 months, met the criteria. There were no significant differences between demographics, risk factors, or initial cyst sizes. Fifty-seven percent of MF dominant cysts and 48% of UF cysts increased in size (P = 0.31). Progression in MF was more likely in the dominant cyst (P < 0.05). There were no significant differences in the development of mural nodules or increase in cyst size to more than 3 cm., Conclusions: Demographics of both cohorts were similar, as was the overall incidence of worrisome features. Because meaningful size progression primarily occurred in the dominant cyst, our findings support surveillance based on the dominant cyst in MF disease.

Context: Molecular analysis of pancreatic cyst fluid obtained by EUS-FNA may increase diagnostic accuracy. We evaluated the utility of cyst-fluid molecular analysis, including mutational analysis of K-ras, loss of heterozygosity (LOH) at tumor suppressor loci, and DNA content in the diagnoses and surveillance of pancreatic cysts., Methods: We retrospectively reviewed the Columbia University Pancreas Center database for all patients who underwent EUS/FNA for the evaluation of pancreatic cystic lesions followed by surgical resection or surveillance between 2006-2011. We compared accuracy of molecular analysis for mucinous etiology and malignant behavior to cyst-fluid CEA and cytology and surgical pathology in resected tumors. We recorded changes in molecular features over serial encounters in tumors under surveillance. Differences across groups were compared using Student's t or the Mann-Whitney U test for continuous variables and the Fisher's exact test for binary variables., Results: Among 40 resected cysts with intermediate-risk features, molecular characteristics increased the diagnostic yield of EUS-FNA (n=11) but identified mucinous cysts less accurately than cyst fluid CEA (P=0.21 vs. 0.03). The combination of a K-ras mutation and ≥2 loss of heterozygosity was highly specific (96%) but insensitive for malignant behavior (50%). Initial data on surveillance (n=16) suggests that molecular changes occur frequently, and do not correlate with changes in cyst size, morphology, or CEA., Conclusions: In intermediate-risk pancreatic cysts, the presence of a K-ras mutation or loss of heterozygosity suggests mucinous etiology. K-ras mutation plus ≥2 loss of heterozygosity is strongly associated with malignancy, but sensitivity is low; while the presence of these mutations may be helpful, negative findings are uninformative. Molecular changes are observed in the course of cyst surveillance, which may be significant in long-term follow-up.

Background: While contemporary studies demonstrate decreasing complication rates following total pancreatectomy (TP), none have quantified the impact of post-TP complications. The Postoperative Morbidity Index (PMI)-a quantitative measure of postoperative morbidity-combines ACS-NSQIP complication data with severity weighting derived from Modified Accordion Grading System. We establish the PMI for TP in a multi-institutional cohort., Methods: Nine institutions contributed ACS-NSQIP data for 64 TPs (2005-2011). Each complication was assigned an Accordion severity weight ranging from 0.110 (grade 1/mild) to 1.00 (grade 6/death). PMI equals the sum of complication severity weights ("Total Burden") divided by total number of patients., Results: Overall, 29 patients (45.3 %) suffered 55 ACS-NSQIP complications; 15 (23.4 %) had >1 complication. Thirteen patients (20.3 %) were readmitted and one death (1.6 %) occurred within 30 days. Non-risk adjusted PMI was 0.151, while PMI for complication-bearing cases rose to 0.333. Bleeding/Transfusion and Sepsis were the most common complications. Discordance between frequency and burden of complications was observed. While grades 4-6 comprised only 18.5 % of complications, they contributed 37.1 % to the series' total burden., Conclusion: This multi-institutional series is the first to quantify the complication burden following TP using the rigor of ACS-NSQIP. A PMI of 0.151 indicates that, collectively, patients undergoing TP have an average burden of complications in the mild to moderate severity range, although complication-bearing patients have a considerable reduction in health utility.

Objective: The study aim was to quantify the burden of complications of pancreatoduodenectomy (PD)., Background: The Postoperative Morbidity Index (PMI) is a quantitative measure of the average burden of complications of a procedure. It is based on highly validated systems--ACS-NSQIP and the Modified Accordion Severity Grading System., Methods: Nine centers contributed ACS-NSQIP complication data for 1589 patients undergoing PD from 2005 to 2011. Each complication was assigned a severity weight ranging from 0.11 for the least severe complication to 1.00 for postoperative death, and PMI was derived. Contribution to total burden by each complication grade was used to generate a severity profile ("spectrogram") for PD. Associations with PMI were determined by regression analysis., Results: ACS-NSQIP complications occurred in 528 cases (33.2%). The non-risk-adjusted PMI was 0.115 (SD = 0.023) for all centers and 0.113 (SD = 0.005) for the 7 centers that contributed at least 100 cases. Grade 2 complications were predominant in frequency, and the most common complication was postoperative bleeding/transfusion. Frequency and burden of complications differed markedly. For instance, severe complications (grades 4/5/6) accounted for only about 20% of complications but for more than 40% of the burden of complications. Organ space infection had the highest burden of any complication. The average burden in cases in which a complication actually occurred was 0.346., Conclusions: This study develops a quantitative non-risk-adjusted benchmark for postoperative morbidity of PD. The method quantifies the burden of types and grades of postoperative complications and should prove useful in identifying areas that require quality improvement.

Background: Accurate assessment of complications is critical in analysing surgical outcomes. The post-operative morbidity index (PMI), derived from the Modified Accordion Severity Grading System and American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP), is a quantitative measure of post-operative morbidity. This study utilizes PMI to establish the complication burden for a distal pancreatectomy (DP)., Methods: From 2005-2011, nine centres contributed ACS-NSQIP complication data for 655 DPs. Each complication was assigned an Accordion severity weight ranging from 0.11 for grade 1 to 1.00 for grade 6 (death). The PMI is the sum of complication severity weights divided by the total number of patients., Results: ACS-NSQIP complications occurred in 177 patients (27.0%). The non risk-adjusted PMI for DP is 0.087. Bleeding/Transfusion and Organ Space Infection were the most common complications. Frequency and burden differed across Accordion grades. While grade 4-6 complications represented only 15.4% of complication occurrences, they accounted for 30.4% of the burden. Subgroup analysis demonstrates that the PMI did not vary based on laparoscopic versus open approach or the performance of a splenectomy., Discussion: This study uses two validated systems to quantitatively establish the morbidity of a DP. The PMI allows estimation of both the frequency and severity of complications and thus provides a more comprehensive assessment of risk., (© 2014 International Hepato-Pancreato-Biliary Association.)

Background: Positron emission tomography (PET) as an adjunct to conventional imaging in the staging of pancreatic adenocarcinoma is controversial. Herein, we assess the utility of PET in identifying metastatic disease and evaluate the prognostic potential of standard uptake value (SUV)., Methods: Imaging and follow-up data for patients diagnosed with pancreatic adenocarcinoma were reviewed retrospectively. Resectability was assessed based on established criteria, and sensitivity, specificity, and accuracy of PET were compared to those of conventional imaging modalities., Results: For 123 patients evaluated 2005-2011, PET and CT/MRI were concordant in 108 (88 %) cases; however, PET identified occult metastatic lesions in seven (5.6 %). False-positive PETs delayed surgery for three (8.3 %) patients. In a cohort free of metastatic disease in 78.9 % of cases, the sensitivity and specificity of PET for metastases were 89.3 and 85.1 %, respectively, compared with 62.5 and 93.5 % for CT and 61.5 and 100.0 % for MRI. Positive predictive value and negative predictive value of PET were 64.1 and 96.4 %, respectively, compared with 75.0 and 88.9 % for CT and 100.0 and 91.9 % for MRI. Average difference in maximum SUV of resectable and unresectable lesions was not statistically significant (5.65 vs. 6.5, p = 0.224) nor was maximum SUV a statistically significant predictor of survival (p = 0.18)., Conclusion: PET is more sensitive in identifying metastatic lesions than CT or MRI; however, it has a lower specificity, lower positive predictive value, and in some cases, can delay definitive surgical management. Therefore, PET has limited utility as an adjunctive modality in staging of pancreatic adenocarcinoma.

Background: Large centralized databases are used with increasing frequency for reporting hospital-specific and nationwide trends and outcomes after various surgical procedures in order to improve quality of surgical care. American College of Surgeons National Surgical Quality Improvement Program (ACS-NSQIP) is a risk-adjusted, case-weighted complication tracking initiative that reports 30-day outcomes from more than 400 academic and community institutions in the US. However, the accuracy of event reporting specific to pancreatic surgery has never been examined in depth., Methods: We retrospectively reviewed medical records of patients, the information on whose postoperative course was originally reported through ACS-NSQIP between 2006 and 2010. Preoperative characteristics, operative data, and postoperative events were recorded after review of electronic medical records including physician and nursing notes, operative room records and anesthesiologist reports. Fidelity of reported clinical events was assessed. Accuracy, sensitivity, and specificity were calculated for each variable of interest., Results: Two hundred and forty-nine pancreatectomies were reviewed, including 145 (58.2 %) Whipple procedures, 19 (7.6 %) total pancreatectomies, 65 (26.1 %) distal pancreatectomies, and 15 (6.0 %) central or partial resections. Median age was 65.7, males comprised 41.5 % of the group, and 74.3 % of patients were Caucasian. The overall rate of complications reported by NSQIP was 44.0 %, compared with 45.0 % in our review, however discordance was observed in 27.3 % of the time, including 34 cases of reporting a complication where there was not one, and 34 cases of missed complication. The most frequently reported event was postoperative bleeding requiring transfusion, however this was also the event most commonly misclassified. Additionally, three procedures unrelated to the index operation were recorded as reoperation events. While a pancreas-specific module does not yet exist, ACS-NSQIP reports a 7.6 % rate of organ-space surgical site infections; when compared with our institutional rate of Grades B and C postoperative fistula (10.4 %), we observed discordance 4.4 % of the time. Delayed gastric emptying, a common post-pancreatectomy morbidity, was not captured at all. Additionally, there were significant inaccuracies in reporting urinary tract infections, postoperative pneumonia, wound complications, and postoperative sepsis, with discordance rates of 4.4, 3.2, 3.6, and 6.8 %, respectively., Conclusions: ACS-NSQIP data are an important and valuable tool for evaluating quality of surgical care, however pancreatectomy-specific postoperative events are often misclassified, underscoring the need for a hepatopancreatobiliary-specific module to better capture key outcomes in this complex and unique patient population.

Background: Neoadjuvant therapy and vascular resection may offer patients with locally advanced pancreatic cancer potential cure., Methods: We reviewed medical records of patients with ductal adenocarcinoma who underwent pancreaticoduodenectomy (PD) from 1992 through 2011. We identified patients who received neoadjuvant therapy (NA+) or required vascular resection (VR+) for locally advanced disease and compared outcomes to those who did not., Results: Of the 643 patients who were initially explored, 506 (143 NA+ and 363 NA- patients) ultimately underwent PD. There were no significant differences in R0 resection or morbidity. Mortality was higher in the NA+ versus NA- group (7.0 vs 3.0 %, p = 0.04). More NA+ patients underwent PD VR+ (p < 0.001). Among VR+ patients, neoadjuvant therapy resulted in significantly lower R1 resection. Among resected patients, survival of NA+ patients was significantly longer than both NA- patients (27.3 vs 19.7 months, p < 0.05) and patients abandoned because of locally advanced disease. Age, tumor grade, lymph node ratio, and R1 resection were independent predictors of poor survival., Conclusions: Neoadjuvant therapy and vascular resection offer patients with locally advanced pancreatic cancer the chance for cure with acceptable morbidity and mortality. These patients have improved survival over patients deemed locally inoperable by traditional criteria.

Background: Laparoscopic retroperitoneal (RP) adrenalectomy has gained popularity as the preferred approach over transabdominal (TA) method; however, surgeons have been reluctant to offer this operation to obese patients because of the concerns over inadequate working space and overall perceived higher rate of complications. The aim of the present study was to evaluate the feasibility and safety of RP adrenalectomy compared with TA adrenalectomy, specifically in morbidly obese patients., Methods: All laparoscopic adrenalectomies performed at our institution between 2004 and 2012 were reviewed retrospectively. Presenting features, operative characteristics, and postoperative outcomes were evaluated. Complications were graded using Clavien system. Continuous variables were compared using Student t-test. Categorical variables were compared using χ(2)-test. Prediction models were constructed using linear or logistic regression as appropriate., Results: Eighty-one RP and 130 TA procedures were performed, 26 (12.3%) and 60 (28.4%), respectively in obese patients (BMI > 30). Among the obese patients, operative time and estimated blood loss were less for RP (90 versus 130 min; P < 0.001 and 0 versus 50 mL; P < 0.001). Differences in the length of stay, overall mortality, incidence and severity of postoperative complications, and rates of readmission were not statistically significant between RP and TA procedures for all comers and in the obese patients. Controlling the operative characteristics and patient-specific factors, neither operative approach nor obesity was found to independently predict the postoperative complications., Conclusions: Laparoscopic RP adrenalectomy is a safe and feasible technique for obese patients. In the obese patients and for all comers, it offers shorter operative time, decreased estimated blood loss, with comparable length of stay and morbidity and mortality rates. We therefore recommend that this technique should be considered for patients undergoing adrenal resection., (Copyright © 2014 Elsevier Inc. All rights reserved.)

Background: Quality of life after total pancreatectomy (TP) is perceived to be poor secondary to insulin-dependent diabetes and pancreatic insufficiency. As a result, surgeons may be reluctant to offer TP for benign and premalignant pancreatic diseases., Methods: We retrospectively reviewed presenting features, operative characteristics, and postoperative outcomes of all patients who underwent TP at our institution. Quality of life was assessed using institutional questionnaires and validated general, pancreatic disease-related, and diabetes-related instruments (European Organization for Research and Treatment of Cancer Quality of Life Questionnaire [EORTC QLQ-C30 and module EORTC-PAN26], Audit of Diabetes Dependent Quality of Life), and compared with frequency-matched controls, patients after a pancreaticoduodenectomy (PD). Continuous variables were compared using Student t-test or analysis of variance. Categorical variables were compared using χ(2) or Fisher exact test., Results: Between 1994 and 2011, 77 TPs were performed. Overall morbidity was 49%, but only 15.8% patients experienced a major complication. Perioperative mortality was 2.6%. Comparing 17 TP and 14 PD patients who returned surveys, there were no statistically significant differences in quality of life in global health, functional status, or symptom domains of EORTC QLQ-C30 or in pancreatic disease-specific EORTC-PAN26. TP patients had slightly but not significantly higher incidence of hypoglycemic events as compared with PD patients with postoperative diabetes. A negative impact of diabetes assessed by Audit of Diabetes Dependent Quality of Life did not differ between TP and PD. Life domains most negatively impacted by diabetes involved travel and physical activity, whereas self-confidence, friendships and personal relationships, motivation, and feelings about the future remained unaffected., Conclusions: Although TP-induced diabetes negatively impacts select activities and functions, overall quality of life is comparable with that of patients who undergo a partial pancreatic resection., (Copyright © 2014. Published by Elsevier Inc.)

Objectives: The purpose of this study was to evaluate the utility of intraoperative sonography of the liver in the staging of pancreatic adenocarcinoma and its impact on the rate of postoperative tumor recurrence in the liver., Methods: We performed a retrospective analysis of the rate in which intraoperative sonography of the liver changed surgical management in 470 surgical candidates with pancreatic adenocarcinoma. In postsurgical patients, we performed a χ(2) analysis to examine whether the patients who underwent hepatic intraoperative sonography had a lower rate of recurrent disease in the liver within the first 6 months of surgery compared to patients who did not undergo the procedure., Results: Hepatic intraoperative sonography affected management in less than 1% of cases, detecting 1 unsuspected liver metastasis in 470 surgical patients with pancreatic adenocarcinoma. Of 3 patients with equivocal liver lesions identified on preoperative computed tomography or magnetic resonance imaging, hepatic intraoperative sonography excluded metastasis and cleared all the patients for surgical resection. There was no significant difference in postoperative liver recurrence between the group of patients who received intraoperative sonography before resection and patients who did not have the procedure done (P > .99)., Conclusions: Routine intraoperative sonography of the liver does not affect staging of pancreatic adenocarcinoma. It may be useful for evaluating equivocal lesions.

Background: Pancreatic surgery with vascular reconstruction is increasingly performed to offer the benefits of surgical resection to patients with locally advanced disease. The short- and long-term patency rates and the clinical significance of thrombosis of such reconstructions are unknown., Methods: We reviewed pancreatectomies requiring venous reconstruction from 1994 to 2011. We sought to identify predictors of acute (within 30 days) and late thrombosis. We compared survival of patients with thrombosis to patients with patent reconstructions., Results: Of 203 pancreatectomies requiring venous reconstruction, acute thrombosis occurred in nine (4.4 %) cases and was associated with increased perioperative mortality (22.2 versus 4.6 %, p = 0.023). Even when nonfatal, acute thrombosis was associated with decreased median survival (7.1 versus 15.9 months, p = 0.011) and increased hazard of death (hazard ratio 8.6, confidence interval 3.7-19.9, p < 0.001). A late loss of patency was seen in 31.2 % of cases at a median of 9.5 months. Later loss of patency was not associated with decreased median survival or increased hazard of death., Conclusions: Acute thrombosis of the portal venous reconstructions after pancreatectomy is associated with increased perioperative mortality and, even when nonfatal, is associated with decreased survival. Late loss of patency occurs in one-third of patients but does not affect survival.

Background: The diagnosis of serous cystadenoma (SCA), a rare benign pancreatic neoplasm, can alter the management of patients with pancreatic masses. Although characteristic imaging findings and fluid chemical analysis have been described, SCAs are not always recognized preoperatively. Furthermore, scant cellular yield on fine-needle aspiration (FNA) often leads to a nondiagnostic or nonspecific benign diagnosis. α-Inhibin (AI), a sensitive marker for SCA, is infrequently required for diagnosis in surgical specimens due to their characteristic histologic appearance. The objective of the current study was to determine whether AI staining can improve SCA diagnosis on FNA specimens., Methods: Fifteen confirmed cases of SCA with prior FNA specimens were selected for this study. FNAs were evaluated for cellularity, cellular arrangement, and cytomorphology. Resection specimens were reviewed., Results: Of the 15 FNA cases, approximately 75% demonstrated scant cellularity (11 of 15 cases). On smears, the cells were arranged as flat sheets, corresponding to strips of cells on cell block sections. The cells were small and round to cuboidal, with clear cytoplasm; occasional plasmacytoid cells and oncocytic cells were identified. Flattened cells, corresponding to attenuated epithelial cells lining macrocysts on the resections, were also noted. Stromal fragments were present in 5 FNAs and correlated with the hyalinized stroma in the resection specimens. AI immunostaining was positive in 88% of cases (7 of 8 of cases), thereby supporting the diagnosis of SCA., Conclusions: The results of the current study indicate that low cellularity and bland cytology are inherent to SCAs. Performing cell blocks and AI staining on FNA specimens is useful for establishing the diagnosis of SCA. An immunohistochemical panel including AI, chromogranin, and synaptophysin may enhance the diagnostic accuracy of pancreatic FNA specimens., (© 2013 American Cancer Society.)

Purpose: Previously, we reported PIK3CA gene mutations in high-grade intraductal papillary mucinous neoplasms (IPMN). However, the contribution of phosphatidylinositol-3 kinase pathway (PI3K) dysregulation to pancreatic carcinogenesis is not fully understood and its prognostic value unknown. We investigated the dysregulation of the PI3K signaling pathway in IPMN and its clinical implication., Experimental Design: Thirty-six IPMN specimens were examined by novel mutant-enriched sequencing methods for hot-spot mutations in the PIK3CA and AKT1 genes. PIK3CA and AKT1 gene amplifications and loss of heterozygosity at the PTEN locus were also evaluated. In addition, the expression levels of PDPK1/PDK1, PTEN, and Ki67 were analyzed by immunohistochemistry., Results: Three cases carrying the E17K mutation in the AKT1 gene and one case harboring the H1047R mutation in the PIK3CA gene were detected among the 36 cases. PDK1 was significantly overexpressed in the high-grade IPMN versus low-grade IPMN (P = 0.034) and in pancreatic and intestinal-type of IPMN versus gastric-type of IPMN (P = 0.020). Loss of PTEN expression was strongly associated with presence of invasive carcinoma and poor survival in these IPMN patients (P = 0.014)., Conclusion: This is the first report of AKT1 mutations in IPMN. Our data indicate that oncogenic activation of the PI3K pathway can contribute to the progression of IPMN, in particular loss of PTEN expression. This finding suggests the potential employment of PI3K pathway-targeted therapies for IPMN patients. The incorporation of PTEN expression status in making surgical decisions may also benefit IPMN patients and should warrant further investigation., (©2013 AACR.)

Background: Intraperitoneal chemotherapy is used to treat peritoneal surface-spreading malignancies. We sought to determine whether volume and surface area of the intraperitoneal chemotherapy compartments are associated with overall survival and posttreatment glomerular filtration rate (GFR) in malignant peritoneal mesothelioma (MPM) patients., Methods: Thirty-eight MPM patients underwent X-ray computed tomography peritoneograms during outpatient intraperitoneal chemotherapy. We calculated volume and surface area of contrast-filled compartments by semiautomated computer algorithm. We tested whether these were associated with overall survival and posttreatment GFR., Results: Decreased likelihood of mortality was associated with larger surface areas (p = 0.0201) and smaller contrast-filled compartment volumes (p = 0.0341), controlling for age, sex, histologic subtype, and presence of residual disease >0.5 cm postoperatively. Larger volumes were associated with higher posttreatment GFR, controlling for pretreatment GFR, body surface area, surface area, and the interaction between body surface area and volume (p = 0.0167)., Discussion: Computed tomography peritoneography is an appropriate modality to assess for maldistribution of intraperitoneal chemotherapy. In addition to identifying catheter failure and frank loculation, quantitative analysis of the contrast-filled compartment's surface area and volume may predict overall survival and cisplatin-induced nephrotoxicity. Prospective studies should be undertaken to confirm and extend these findings to other diseases, including advanced ovarian carcinoma.

Objectives: We examined long-term outcomes in patients with surgically treated intraductal papillary mucinous neoplasm (IPMN) to determine if any clinical or histologic features could predict risk of recurrent disease., Methods: We reviewed 183 margin-negative surgical resections performed for IPMN between 1994 and 2011 with documented postoperative abdominal imaging. We calculated time to recurrent disease as indicated by radiographic change and created a multivariable Cox proportional hazards model to assess the relationship between patient characteristics and histopathologic tumor features and disease recurrence., Results: Among patients with margin-negative resections and adequate imaging follow-up, we observed a recurrence rate of 13% over a median follow-up of 32.0 months. Individuals with invasive tumors on original pathology were more likely to recur (HR 5.2, 95% CI 2.2-12.2); however, original pathology did not predict disease severity on recurrence. Controlling for invasive pathology, no other histologic feature of the original tumor, including dysplasia at the surgical margin, predicted recurrence. Among non-invasive IPMN, pancreatitis was associated with disease recurrence (HR 3.6, 95% CI 1.2-10.7)., Conclusions: The frequency of recurrent disease in this population and the inability to predict recurrence argues for universal and continuous surveillance after resection for IPMN. The relationship between pancreatitis and disease recurrence should be investigated further.

Importance: Research has been limited on the incidence, mechanisms, etiology, and treatment of symptoms that require palliation in patients with terminal cancer. Bowel obstruction (BO) is a common complication of advanced abdominal cancer, including colon cancer, for which small, single-institution studies have suggested an incidence rate of 15% to 29%. Large population-based studies examining the incidence or risk factors associated with BO in cancer are lacking., Objective: To investigate the incidence and risk factors associated with BO in patients with stage IV colon cancer., Design and Setting: Retrospective cohort, population-based study of patients in the Surveillance, Epidemiology, and End Results and Medicare claims linked databases who were diagnosed as having stage IV colon cancer from January 1, 1991, through December 31, 2005., Patients: Patients 65 years or older with stage IV colon cancer (n = 12 553)., Main Outcomes and Measures: Time to BO, defined by inpatient hospitalization for BO. We used Cox proportional hazards regression models to determine associations between BO and patient, prior treatment, and tumor features., Results: We identified 1004 patients with stage IV colon cancer subsequently hospitalized with BO (8.0%). In multivariable analysis, proximal tumor site (hazard ratio, 1.22 [95% CI, 1.07-1.40]), high tumor grade (1.34 [1.16-1.55]), mucinous histological type (1.27 [1.08-1.50]), and nodal stage N2 (1.52 [1.26-1.84]) were associated with increased risk of BO, as was the presence of obstruction at cancer diagnosis (1.75 [1.47-2.04]). A more recent diagnosis was associated with decreased risk of subsequent obstruction (hazard ratio, 0.84 [95% CI, 0.72-0.98])., Conclusions and Relevance: In this large population of patients with stage IV colon cancer, BO after diagnosis was less common (8.0%) than previously reported. Risk was associated with site and histological type of the primary tumor. Future studies will explore management and outcomes in this serious, common complication.

Background: Bowel obstruction is a common complication of late-stage abdominal cancer, especially colon cancer, which has been investigated predominantly in small, single-institution studies., Objective: We used a large, population-based data set to explore the surgical treatment of bowel obstruction and its outcomes after hospitalization for obstruction among patients with stage IV colon cancer., Design: This was a retrospective cohort study., Setting and Patients: We identified 1004 patients aged 65 years or older in the Surveillance, Epidemiology and End Results-Medicare database diagnosed with stage IV colon cancer January 1, 1991 to December 31, 2005, who were later hospitalized for bowel obstruction., Main Outcome Measures: We describe outcomes after hospitalization and analyzed the associations between surgical treatment of obstruction and outcomes., Results: Hospitalization for bowel obstruction occurred a median of 7.4 months after colon cancer diagnosis, and median survival after obstruction was approximately 2.5 months. Median hospitalization for obstruction was about 1 week and in-hospital mortality was 12.7%. Between discharge and death, 25% of patients were readmitted to the hospital at least once for obstruction, and, on average, patients lived 5 days out of the hospital for every day in the hospital between obstruction diagnosis and death. Survival was 3 times longer in those whose obstruction claims suggested an adhesive obstruction origin. In multivariable models, surgical compared with nonsurgical management was not associated with prolonged survival (p = 0.134)., Limitations: Use of an administrative database did not allow determination of quality of life or relief of obstruction as an outcome, nor could nonsurgical interventions, eg, endoscopic stenting or octreotide, be assessed., Conclusions: In this population-based study of patients with stage IV colon cancer who had bowel obstruction, overall survival following obstruction was poor irrespective of treatment. Universally poor outcomes suggest that a diagnosis of obstruction in the setting of advanced colon cancer should be considered a preterminal event.

Background: Hospital readmission has been proposed as a metric for quality of medical and surgical care. We examined our institutional experience with readmission after pancreatic resection, and assessed factors predictive of readmission., Methods: We reviewed 787 pancreatic resections performed at a single institution between 2006 and 2010. Univariate and multivariate logistic regression models were used to assess the relationships between preoperative and postoperative characteristics and readmission. Reasons for hospital readmission were examined in detail., Results: We found the 30-day readmission rate after pancreatic resection to be 11.6 %. In univariate analysis, young age, pancreaticoduodenectomy versus other operations, open versus laparoscopic technique, fistula formation, the need for reoperation, and any complication during the index hospitalization were predictive of readmission. In multivariate analysis, only young age and postoperative complication were predictive of readmission. Vascular resection, postoperative ICU care, length of stay, and discharge disposition were not associated with readmission. The most common reasons for readmission were leaks, fistulas, abscesses, and wound infections (45.1 %), delayed gastric emptying (12.1 %), venous thrombosis (7.7 %), and GI bleeding (7.7 %)., Conclusions: We found the vast majority of readmissions after pancreatic resection were to manage complications related to the operation and were not due to poor coordination of care or poor discharge planning. Because evidence-based measures to prevent these surgical complications do not exist, we cannot support the use of readmission rates themselves as a quality indicator after pancreatic surgery.

Background: Few formal cost-effectiveness analyses simultaneously evaluate radiographic, endoscopic, and surgical approaches to the management of choledocholithiasis., Study Design: Using the decision analytic software TreeAge, we modeled the initial clinical management of a patient presenting with symptomatic cholelithiasis without overt signs of choledocholithiasis. In this base case, we assumed a 10 % probability of concurrent asymptomatic choledocholithiasis. Our model evaluated four diagnostic/therapeutic strategies: universal magnetic resonance cholangiopancreatography (MRCP), universal endoscopic retrograde cholangiopancreatography (ERCP), laparoscopic cholecystectomy (LC), or laparoscopic cholecystectomy with universal intraoperative cholangiogram (LCIOC). All probabilities were estimated from a review of published literature. Procedure and intervention costs were equated with Medicare reimbursements. Costs of hospitalizations were derived from median hospitalization reimbursement for New York State using diagnosis-related groups (DRG). Sensitivity analyses were performed on all cost and probability variables., Results: The most cost-effective strategy in the diagnosis and management of symptomatic cholelithiasis with a 10 % risk of asymptomatic choledocholithiasis was LCIOC. This was followed by LC alone, MRCP, and ERCP. LC was preferred only when the probability that a retained CBD stone would eventually become symptomatic fell below 15 % or if the probability of technical success of an intraoperative cholangiogram (IOC) was less than 35 %. Universal MRCP and ERCP were both more costly and less effective than surgical strategies, even at a high probability of asymptomatic choledocholithiasis. Within the tested range for both procedural and hospitalization-related costs for any of the surgical or endoscopic interventions, LCIOC and LC were always more cost-effective than universal MRCP or ERCP, irrespective of the presence or absence of complications. Varying the cost, sensitivity, and specificity of MRCP had no effect on this outcome., Conclusions: LC with routine IOC is the preferred strategy in a cost-effectiveness analysis of the management of symptomatic cholelithiasis with asymptomatic choledocholithiasis. MRCP was both more costly and less effective under all tested scenarios.

Purpose: Bowel obstruction is a common pre-terminal event in abdominal/pelvic cancer that has mainly been described in small single-institution studies. We used a large, population-based database to investigate the incidence, management, and outcomes of obstruction in ovarian cancer patients., Patients and Methods: We identified patients with stages IC-IV ovarian cancer, aged 65 years or older, in the Surveillance, Epidemiology and End Results (SEER)-Medicare database diagnosed between January 1, 1991 and December 31, 2005. We modeled predictors of inpatient hospitalization for bowel obstruction after cancer diagnosis, categorized management of obstruction, and analyzed the associations between treatment for obstruction and outcomes., Results: Of 8607 women with ovarian cancer, 1518 (17.6%) were hospitalized for obstruction subsequent to cancer diagnosis. Obstruction at cancer diagnosis (HR=2.17, 95%CI: 1.86-2.52) and mucinous tumor histology (HR=1.45, 95%CI: 1.15-1.83) were associated with increased risk of subsequent obstruction. Surgical management of obstruction was associated with lower 30-day mortality (13.4% in women managed surgically vs. 20.2% in women managed non-surgically), but equivalent survival after 30 days and equivalent rates of post-obstruction chemotherapy. Median post-obstruction survival was 382 days in women with obstructions of adhesive origin and 93 days in others., Conclusion: In this large-scale, population-based assessment of patients with advanced ovarian cancer, nearly 20% of women developed bowel obstruction after cancer diagnosis. While obstruction due to adhesions did not signal the end of life, all other obstructions were pre-terminal events for the majority of patients regardless of treatment., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: Hyperthermic intraoperative intraperitoneal chemotherapy (HIPEC) is used to treat peritoneal surface-spreading malignancies to maximize local drug concentrations while minimizing systemic effects. The pharmacokinetic advantage of HIPEC is defined as the intraperitoneal to intravascular ratio of drug concentrations. We hypothesized that body surface area (BSA) would correlate with the pharmacokinetic advantage of HIPEC. Because oxaliplatin is administered in 5 % dextrose, we hypothesized that BSA would correlate with glycemia., Methods: We collected blood and peritoneal perfusate samples from ten patients undergoing HIPEC with a BSA-based dose of 250 mg/m(2) oxaliplatin, and measured drug concentrations by inductively coupled plasma mass spectrophotometry. We monitored blood glucose for 24 h postoperatively. Areas under concentration-time curves (AUC) were calculated by trapezoidal rule. Pharmacokinetic advantage was calculated by (AUC[peritoneal fluid]/AUC[plasma]). We used linear regression to test for statistical significance., Results: Higher BSA was associated with lower plasma oxaliplatin AUC (p = 0.0075) and with a greater pharmacokinetic advantage (p = 0.0198) over the 60-minute duration of HIPEC. No statistically significant relationships were found between BSA and blood glucose AUC or peak blood glucose levels., Conclusions: Higher BSA is correlated with lower plasma drug levels and greater pharmacokinetic advantage in HIPEC, likely because of increased circulating blood volume with inadequate time for equilibration. Plasma glucose levels after oxaliplatin HIPEC were not clearly related to BSA.

Accurate staging of pancreatic adenocarcinoma is a crucial step in determining the appropriate therapeutic approach to pancreatic cancer and to maximizing life expectancy. Despite the availability of high-quality abdominal imaging, the use of multi-modality imaging and of diagnostic laparoscopy, a portion of surgically explored patients fail to undergo resection secondary to metastatic disease. This review is an update from the 2012 American Society of Clinical Oncology (ASCO) Gastrointestinal Cancers Symposium of new developments in the staging of localized pancreatic adenocarcinoma. (Abstracts #168, #177, and #212).

Background: The receptor for advanced glycation end-products (RAGE) is implicated in pancreatic tumorigenesis. Activating Kras mutations and p16 inactivation are genetic abnormalities most commonly detected as pancreatic ductal epithelium progresses from intraepithelial neoplasia (PanIN) to adenocarcinoma (PDAC)., Objective: The aim of this study was to evaluate the effect of RAGE (or AGER) deletion on the development of PanIN and PDAC in conditional Kras ( G12D ) mice., Materials and Methods: Pdx1-Cre; LSL-Kras ( G12D/+) mice were crossed with RAGE (-/-) mice to generate Pdx1-Cre; LSL-Kras ( G12D/+) ; RAGE (-/-) mice. Pdx1-Cre; LSL-Kras ( G12D/+); p16 ( Ink4a-/-) mice were crossed with RAGE (-/-) mice to generate Pdx1-Cre; LSL-Kras ( G12D/+); p16 ( Ink4a-/-); RAGE (-/-) mice. Pancreatic ducts were scored and compared to the relevant RAGE (+/+) controls., Results: At 16 weeks of age, Pdx1-Cre; LSL-Kras ( G12D/+); RAGE (-/-) mice had significantly fewer high-grade PanIN lesions than Pdx1-Cre; LSL-Kras ( G12D/+); RAGE (+/+) controls. At 12 weeks of age, none of the Pdx1-Cre; LSL-Kras ( G12D/+); p16 ( Ink4a-/-); RAGE (-/-) mice had PDAC compared to a 45.5% incidence of PDAC in Pdx1-Cre; LSL-Kras ( G12D/+); p16 ( Ink4a-/-); RAGE (+/+) controls. Finally, Pdx1-Cre; LSL-Kras ( G12D/+); p16 ( Ink4a-/-); RAGE (-/-) mice also displayed markedly longer median survival., Conclusion: Loss of RAGE function inhibited the development of PanIN and progression to PDAC and significantly prolonged survival in these mouse models. Further work is needed to target the ligand-RAGE axis for possible early intervention and prophylaxis in patients at risk for developing pancreatic cancer.

Background: Studies suggest that while most pediatric thyroid nodules are benign, there is a higher rate of malignancy than in adults. We investigate clinical factors that may predict malignancy in pediatric thyroid nodules., Methods: A retrospective review of 207 pediatric thyroidectomies was conducted over 15 years at 2 tertiary hospitals. Analyses examined predictive values of 16 clinicopathologic factors associated with cancer. Positive predictive values (PPVs) of fine-needle aspiration biopsy specimens (FNABs) were analyzed independently., Results: Malignancy occurred in 41% of patients. After excluding missing data, malignancy was more likely with family history of thyroid cancer (34.2% vs 17.7%; P = .111), palpable lymphadenopathy (34.2% vs 2.9%; P = .001), and hypoechoic nodules (52.2% vs 19.2%; P = .016). Palpable lymphadenopathy indicated greater than 2-fold increased risk for malignancy (relative risk, 2.18; 95% confidence interval, 1.56-3.05). PPVs of FNAB results were 0.94 for malignancy, 0.63 for suspicious for malignancy, and 0.55 for indeterminate lesions. PPV for benign FNAB to be benign on final pathology was 0.71., Conclusion: While malignancy is associated with family history of thyroid cancer and hypoechoic lesions, palpable lymphadenopathy had the greatest risk. When compared to adults, a benign FNAB in children is not as accurate and the likelihood that an indeterminate nodule is cancer is greater., (Copyright © 2011 Mosby, Inc. All rights reserved.)

Background: Traditional resections for benign and low-grade malignant neoplasms of the mid pancreas result in loss of normal parenchyma that can cause pancreatic endocrine and exocrine insufficiency. Central pancreatectomy (CP) is a parenchyma-sparing option for such lesions. This study evaluates a single institution's experience with CP and compares outcomes with distal pancreatectomy (DP)., Methods: We retrospectively collected data on CP patients from 1997 through 2009 and evaluated outcomes. In a subset of 50 patients, we performed a matched-pairs analysis to directly compare the short- and long-term outcomes of CP and DP., Results: Seventy-three patients underwent CP with a median operating room time of 254 minutes. Overall morbidity was 41.1% with pancreatic fistula in 20.5%. Mortality was 0%. There were no differences in fistula, morbidity, and mortality rates between the CP and DP groups. The CP group had resected for smaller lesions. CP patients had a lower rate of new-onset and worsening diabetes than DP patients (14% vs 46%; P = .003). Of new-onset and worsening diabetics, only 1 CP patient required insulin compared with 14 DP patients (P = .002)., Conclusion: CP is safe and effective for select neoplasms of the mid pancreas. Patients undergoing CP have markedly decreased insulin requirements compared with DP patients., (Copyright © 2010 Mosby, Inc. All rights reserved.)

Background: Most experts agree that primary hyperaldosteronism (PHA) caused by an aldosterone-producing adenoma (APA) is best treated by adrenalectomy. From a public health standpoint, the cost of treatment must be considered. We sought to compare the current guideline-based (surgical) strategy with universal pharmacologic management to determine the optimal strategy from a cost perspective., Methods: A decision analysis was performed using a Markov state transition model comparing the strategies for PHA treatment. Pharmacologic management for all patients with PHA was compared with a strategy of screening for and resecting an aldosterone-producing adenoma. Success rates were determined for treatment outcomes based on a literature review. Medicare reimbursement rates were calculated to estimate costs from a third-party payer perspective., Results: Screening for and resecting APAs was the least costly strategy in this model. For a reference patient with 41 remaining years of life, the discounted expected cost of the surgical strategy was $27,821. The discounted expected cost of the medical strategy was $34,691. The cost of adrenalectomy would have to increase by 156% to $22,525 from $8,784 for universal pharmacologic therapy to be less costly. Screening for APA is more costly if fewer than 9.6% of PHA patients have resectable APA., Conclusion: Resection of APAs was the least costly treatment strategy in this decision analysis model., (Copyright © 2010 Mosby, Inc. All rights reserved.)

Background: The receptor for advanced glycation end-products (RAGE) is a cell surface receptor implicated in tumor cell proliferation and migration. We hypothesized that RAGE signaling impacts tumorigenesis and metastatic tumor growth in murine models of colorectal carcinoma., Materials and Methods: Tumorigenesis: Apc (1638N/+) mice were crossed with Rage (-/-) mice in the C57BL/6 background to generate Apc (1638N/+)/Rage (-/-) mice. Metastasis: BALB/c mice underwent portal vein injection with CT26 cells (syngeneic) and received daily soluble (s)RAGE or vehicle. Rage (-/-) mice and Rage (+/+) controls underwent portal vein injection with MC38 cells (syngeneic). Rage (+/+) mice underwent portal vein injection with MC38 cells after stable transfection with full-length RAGE or mock transfection control., Results: Tumorigenesis: Apc (1638N/+)/Rage (-/-) mice had reduced tumor incidence, size, and histopathologic grade. Metastasis: Pharmacological blockade of RAGE with sRAGE or genetic deletion of Rage reduced hepatic tumor incidence, nodules, and burden. Gain of function by transfection with full-length RAGE increased hepatic tumor burden compared to vector control MC38 cells., Conclusion: RAGE signaling plays an important role in tumorigenesis and hepatic tumor growth in murine models of colorectal carcinoma. Further work is needed to target the ligand-RAGE axis for possible prophylaxis and treatment of primary and metastatic colorectal carcinoma.

Background: Uncertainties remain over whether prophylactic surgery or surveillance is the better management option for intraductal papillary mucinous neoplasm of the pancreas. The aim of this preliminary study was to determine if differences in anxiety and quality of life exist between patients who have surgery or undergo surveillance., Methods: Recruited patients were given the Hospital Anxiety and Depression Scale, a general survey that evaluates anxiety, and the Functional Assessment of Cancer Therapy-Pancreas, a disease-specific survey that assesses quality of life. Questionnaires were scored by standardized algorithms and compared using Student's t test or Wilcoxon rank-sum test., Results: Sixteen patients had surgery and 16 patients were undergoing surveillance. Mean age was 66.8 ± 19.9 years. Responses from both groups were remarkably similar. Surgery patients scored higher on the anxiety questionnaire than surveillance patients, although not statistically significant (p = 0.09). Surgery patients scored lower on the functional well-being domain of the quality-of-life instrument (p = 0.03), though there were no differences in overall quality of life., Conclusion: Prophylactic surgery does not reduce quality of life, and a protocol of surveillance does not appear to generate undue anxiety in this select patient group. Further investigation with more patients is required to validate these findings.

Background: Surgery offers the only chance for cure in patients with pancreatic cancer, and a growing number of elderly patients are being offered resection. We examined outcomes after pancreaticoduodenectomy in patients 80 years and older., Methods: We retrospectively collected data on pancreaticoduodenectomy patients from 1992 to 2009 to compare outcomes between patients older and younger than 80 years. Variables were compared using t-, Wilcoxon rank-sum, or Fisher's exact tests. Survival was compared using Kaplan-Meier analysis and log-rank test., Results: Patients 80 years and older who underwent pancreaticoduodenectomy were similar with respect to sex, race, blood loss, operative times, reoperation, length of stay, and readmission compared to younger patients. There were no differences in overall complications (47% vs. 51%, p = 0.54), major complications (19% vs. 25%, p = 0.25), and mortality (5% vs. 4%, p = 0.53) when comparing older to younger patients. In a subset who underwent pancreaticoduodenectomy for ductal adenocarcinoma, older patients (n = 45) had a median survival time of 11.6 months compared to 18.1 months in younger patients (n = 346; p < 0.01)., Conclusion: Pancreaticoduodenectomy can be performed safely in select patients 80 years and older. Age alone should not dissuade surgeons from offering patients resection, though elderly patients with pancreatic ductal adenocarcinoma appear to have shorter survival than younger patients with the same disease.

Background: Laparoscopic distal pancreatectomy (LDP) is increasingly performed for lesions of the body and tail of the pancreas. The aim of this study was to investigate short-term outcomes after LDP compared to open distal pancreatectomy (ODP) at a single, high-volume institution., Methods: We reviewed records of patients who underwent distal pancreatectomy (DP) and compared perioperative data between LDP and ODP. Continuous variables were compared using Student's t or Wilcoxon rank-sum tests. Categorical variables were compared using chi-square or Fisher's exact test., Results: A total of 360 patients underwent DP. Beginning in 2001, 95 were attempted, and 71 were completed laparoscopically with a 25.3% conversion rate. Compared to ODP, LDP had similar rates of splenic preservation, pancreatic fistula, and mortality. LDP had lower blood loss (150 vs. 900 mL, p < 0.01), smaller tumor size (2.5 vs. 3.6 cm, p < 0.01), and shorter length of resected pancreas (7.7 vs. 10.0 cm, p < 0.01). LDP had fewer complications (28.2% vs. 43.8%, p = 0.02) as well as shorter hospital stays (5 vs. 6 days, p < 0.01)., Conclusions: LDP can be performed safely and effectively in patients with benign or low-grade malignant neoplasms of the distal pancreas. When feasible in selected patients, LDP offers fewer complications and shorter hospital stays.

Background: Increasingly, surgeons apply minimally invasive and parenchyma-sparing techniques to the management of pancreatic neuroendocrine tumor (PNET). The aim of this study was to evaluate the impact of these approaches on patient outcomes., Methods: We retrospectively collected data on patients with PNET and compared perioperative and pathologic variables. Survival was analyzed using the Kaplan-Meier method. Factors influencing survival were evaluated using a Cox proportional hazards model., Results: One hundred thirty patients underwent resection for PNET. Traditional resections included 43 pancreaticoduodenectomies (PD), 38 open distal pancreatectomies (DP), and four total pancreatectomies. Minimally invasive and parenchyma-sparing resections included 25 laparoscopic DP, 11 central pancreatectomies, five enucleations, three partial pancreatectomies, and one laparoscopic-assisted PD. Compared to traditional resections, the minimally invasive and parenchyma-sparing resections had shorter hospital stays. By univariate analysis of neuroendocrine carcinoma, liver metastases and positive resection margins correlated with poor survival. There was an increase in minimally invasive or parenchyma-sparing resections over the study period with no differences in morbidity, mortality, or survival., Conclusion: In this series, there has been a significant increase in minimally invasive and parenchyma-sparing techniques for PNET. This shift did not increase morbidity or compromise survival. In addition, minimally invasive and parenchyma-sparing operations yielded shorter hospital stays.

Background: Patients are relying on the Internet with greater frequency to learn about diseases and make medical decisions. We hypothesized that there is a disparity between the perceptions of patients and those of surgeons regarding the quality of information about primary hyperparathyroidism on the Internet., Methods: Patients (n = 62) with primary hyperparathyroidism seen in endocrine surgery clinics in France and the United States responded to a survey regarding their use of the Internet to prepare for upcoming parathyroid surgery. A panel of endocrine surgeons reviewed the top "hits" retrieved from Web sites related to parathyroid disease. Sites were rated using a previously validated Web site quality scoring system., Results: A total of 75% of the American cohort and 53% of the French cohort used the Internet to prepare for parathyroid surgery. The majority of these patients reported that the information was "somewhat to very accurate." The panel of surgeons gave the Web sites an overall average qualitative score of 8.6 (53%)., Conclusion: Surgeons and patients have different perceptions as to what constitutes a high-quality Web site. As patients depend more on the Internet to prepare for parathyroid surgery, there is an opportunity and a clear need to create comprehensive, high-quality, patient-oriented Web sites on this topic.

Background: Mutations of KRAS are known to occur in periampullary and ampullary adenomas and carcinomas. However, nothing is known about NRAS, HRAS, BRAF, and PIK3CA mutations in these tumors. While oncogenic BRAF contributes to the tumorigenesis of both pancreatic ductal adenocarcinoma and intraductal papillary mucinous neoplasms/carcinomas (IPMN/IPMC), PIK3CA mutations were only detected in IPMN/IPMC. This study aimed to elucidate possible roles of BRAF and PIK3CA in the development of ampullary and periampullary adenomas and carcinomas., Methods: Mutations of BRAF, NRAS, HRAS, KRAS, and PIK3CA were evaluated in seven adenomas, seven adenomas with carcinoma in situ, and 21 adenocarcinomas of the periampullary duodenal region and the ampulla of Vater. Exons 1 of KRAS; 2 and 3 of NRAS and HRAS; 5, 11, and 15 of BRAF; and 9 and 20 of PIK3CA were examined by direct genomic sequencing., Results: In total, we identified ten (28.6%) KRAS mutations in exon 1 (nine in codon 12 and one in codon 13), two missense mutations of BRAF (6%), one within exon 11 (G469A), and one V600E hot spot mutation in exon 15 of BRAF. BRAF mutations were present in two of five periampullary tumors. All mutations appear to be somatic since the same alterations were not detected in the corresponding normal tissues., Conclusion: Our data provide evidence that oncogenic properties of KRAS and BRAF but not NRAS, HRAS, and PIK3CA contribute to the tumorigenesis of periampullary and ampullary tumors; BRAF mutations occur more frequently in periampullary than ampullary neoplasms.

Background: The arterial anatomy supplying the liver is highly variable. One of the most common variants is a completely replaced right hepatic artery which is seen in about 11% of the population. Interruption of arterial flow to the right hepatic artery at the time of pancreaticoduodenectomy has been associated with biliary fistula and the consequent complications, as well as stenosis of the biliary enteric anastomosis. Malignancies of the posterior aspect of the head of the pancreas can encase a replaced right hepatic artery without involvement of other vascular structures. In this situation, it is possible to resect and reconstruct the replaced right hepatic artery to maintain oxygen delivery to the biliary enteric anastomosis., Summary: Herein we describe a technique to reconstruct a replaced right hepatic artery following resection of the vessel en bloc with the tumor during a pancreaticoduodenectomy, using inflow from the gastroduodenal artery.

Unlabelled: CONTEX: Most cases of pancreatoblastoma, a rare tumor of neuroendocrine origin, are seen in the pediatric population. To date, at least sixteen case reports have been described of pancreatoblastoma in patients 19-year old or older. Surgical resection is the mainstay of curative treatment. Even patients with liver metastasis can have long-term disease-free survival., Case Report: One recent example is a 33-year-old male who presented to us for a right hepatic lobectomy for removal of the presumed primary tumor - later discovered to be a metastasis - followed by pancreaticoduodenectomy for resection of the true primary lesion. Five years after resection, this patient is the longest disease-free survivor of metastatic adult pancreatoblastoma., Conclusion: We review the literature and propose that resection of pancreatoblastoma can offer long-term disease-free survival even with liver metastasis and microscopically-positive surgical margins.

Objective: There is much accumulated evidence that EGFR, HER2, and their downstream signaling pathway members such as KRAS, BRAF, and PIK3CA are strongly implicated in cancer development and progression. Recently, mutations in the kinase domains of EGFR and HER2, associated with increased sensitivity to tyrosine kinase inhibitors, have been described., Methods: To evaluate the mutational status of these genes in intraductal papillary mucinous neoplasm (IPMN)/intraductal papillary mucinous carcinoma (IPMC), EGFR and HER2 were analyzed in 36 IPMN/IPMC, and the results were correlated to the mutational status of the KRAS, BRAF, and PIK3CA genes in the samples., Results: Together, we identified 1 silent mutation of HER2, 17 (43%) KRAS mutations, 1 (2.7%) BRAF mutation, and 4 (11%) mutations of PIK3CA in the IPMN/IPMC samples., Conclusions: The EGFR and ERBB2 (HER2) mutations are very infrequent in IPMN/IPMC, suggesting the limited possibility of targeting mutated ERBB2 and EGFR for therapy for these lesions. The KRAS, BRAF, and PIK3CA, however, could represent interesting targets for future therapies in these lesions.

Background: We evaluated the feasibility and efficacy of neoadjuvant chemotherapy and radiation for patients with locally unresectable pancreatic cancer., Materials and Methods: From October 2000 to August 2006, 245 patients with pancreatic adenocarcinoma underwent surgical exploration at our institution. Of these, 78 patients (32%) had undergone neoadjuvant therapy for initially unresectable disease, whereas the remaining patients (serving as the control group) were explored at presentation (n=167). All neoadjuvant patients received gemcitabine-based chemotherapy, often in conjunction with docetaxal and capecitabine in a regimen called GTX (81%). Seventy-five percent of neoadjuvant patients also received preoperative abdominal radiation (5,040 rad)., Results: Neoadjuvant patients were younger than control-group patients (60.8 vs 66.2 years, respectively, p<0.002). Seventy-six percent of neoadjuvant patients were resected as compared to 83% of control patients (NS). Concomitant vascular resection was required in 76% of neoadjuvant patients but only 20% of NS (p<0.01). Complications were more frequent in the neoadjuvant group (44.1 vs 30.9%, p<0.05), and mortality was higher (10.2 vs 2.9%, p<0.03). Among the neoadjuvant patients, all but one of the deaths were in patients that underwent arterial reconstruction. Mortality for patients undergoing a standard pancreatectomy without vascular resection was 0.8% in this series. Of patients resected, negative margins were achieved in 84.7% of neoadjuvant patients and 72.7% of NS. Within the cohort of neoadjuvant patients, radiation significantly increased the complication rate (13.3 vs 54.6%, p<0.006), but did not affect median survival (512 vs 729 days, NS). Median survival for patients who received neoadjuvant therapy (503 days) was longer than NS that were found to be unresectable at surgery (192 days, p<0.001) and equivalent to NS that were resected (498 days)., Conclusions: Resection rate, margin status, and median survivals were equivalent when neoadjuvant patients were compared to patients considered resectable by traditional criteria, demonstrating equal efficacy. Surgical resection with venous reconstruction following neoadjuvant therapy for patients with locally advanced pancreatic cancer can be performed with acceptable morbidity and mortality. This approach extended the boundaries of surgical resection and greatly increased median survival for the "inoperable" patient with advanced pancreatic cancer.

The Raf/MEK/ERK (MAPK) signal transduction is an important mediator of a number of cellular fates including growth, proliferation, and survival. The BRAF gene is activated by oncogenic RAS, leading to cooperative effects in cells responding to growth factor signals. Our study was performed to elucidate a possible role of BRAF in the development of IPMN (Intraductal Papillary Mucinous Neoplasm) and IPMC (Intraductal Papillary Mucinous Carcinoma) of the pancreas. Mutations of BRAF and KRAS were evaluated in 36 IPMN/IPMC samples and two mucinous cystadenomas by direct genomic sequencing. Exons 1 for KRAS, and 5, 11, and 15 for BRAF were examined. Totally we identified 17 (47%) KRAS mutations in exon 1, codon 12 and one missense mutation (2.7%) within exon 15 of BRAF. The mutations appear to be somatic since the same alterations were not detected in the corresponding normal tissues. Our data provide evidence that oncogenic properties of BRAF contribute to the tumorigenesis of IPMN/IPMC, but at a lower frequency than KRAS.

Introduction: Patients undergoing partial pancreatectomy are at risk for developing surgically induced diabetes. Patients with lesions in the neck and body of the pancreas are at increased risk because traditional resectional approaches (pancreaticoduodenectomy or distal pancreatectomy) must be extended to remove the tumor with adequate margins. Increasingly, we have been performing pancreatic parenchyma-sparing resections (central pancreatectomy with pancreaticogastrostomy) in an effort to reduce the risk of postpancreatectomy endocrine insufficiency., Methods: The operative records of patients who underwent pancreatectomy at our institution from 1999 to 2005 were reviewed. We identified 26 patients who underwent central pancreatectomy with pancreaticogastrostomy reconstruction for cystic lesions (n = 23), neuroendocrine tumors (n = 2), and Frantz's tumor (n = 1). Charts were reviewed for patient demographics, volume of resection, complications, and evaluation of postoperative glycemic control., Results: The mean follow-up was 33 months (range 3-72 months). The average volume of pancreas resected was 49.6 +/- 38.6 cm(3), and the mean diameter of the lesions was 2.6 +/- 1.5 cm. Nine complications occurred in eight patients (overall morbidity 31%), and the average length of stay was 6.9 +/- 2.7 days. Pancreatic leaks (n = 2; 7.7%) were successfully managed nonoperatively. There was no operative mortality, and there has been no tumor recurrence. None of the patients were diabetic preoperatively. Postoperatively, two (7.7%) developed endocrine insufficiency with a mean postoperative hemoglobin A1c (HbA1c) value of 7.65%. Neither patient has required exogenous insulin. HbA1c in the remaining patients was 5.9% +/- 0.5%., Conclusions: Pancreatic parenchyma-sparing surgery for lesions in the midportion of the gland can be performed with acceptable morbidity. Postoperative glycemic control after pancreatic parenchyma-sparing surgery compares favorably with that reported for patients with traditional resections.

Purpose: Recent studies have reported high frequencies of somatic mutations in the phosphoinositide-3-kinase catalytic-alpha (PIK3CA) gene in various human solid tumors. More than 75% of those somatic mutations are clustered in the helical (exon 9) and kinase domains (exon 20). The three hot-spot mutations, E542K, E545K, and H1047R, have been proven to elevate the lipid kinase activity of PIK3CA and activate the Akt signaling pathway. The mutational status of PIK3CA in intraductal papillary mucinous neoplasm/carcinoma (IPMN/IPMC) has not been evaluated previously., Experimental Design: To evaluate a possible role for PIK3CA in the tumorigenesis of IPMN and IPMC, exons 1, 4, 5, 6, 7, 9, 12, 18, and 20 were analyzed in 36 IPMN/IPMC and two mucinous cystadenoma specimens by direct genomic DNA sequencing., Results: We identified four missense mutations in the nine screened exons of PIK3CA from 36 IPMN/IPMC specimens (11%). One of the four mutations, H1047R, has been previously reported as a hot-spot mutation. The remaining three mutations, T324I, W551G, and S1015F, were novel and somatic., Conclusion: This is the first report of PIK3CA mutation in pancreatic cancer. Our data provide evidence that the oncogenic properties of PIK3CA contribute to the tumorigenesis of IPMN/IPMC.

This article reviews the relevant literature and reports on The Columbia University Medical Center experience with chemoradiation for pancreatic cancer.